The Research Grant Program stimulates epilepsy research by providing funding for investigators in the early stages of their careers. Seed grants are awarded to clinical investigators or basic scientists for support of biological or behavioral research which will advance the understanding, treatment, and prevention of epilepsy. Applications from established investigators (Associate Professor level or above) are ineligible.

One- and two-year Research Grants fund clinical and laboratory investigators in the early stages of their careers. Established researchers are ineligible for the grants, which seed studies in biology and behavior to advance understanding, treatment, and prevention of epilepsy. This Fall's Research Grants will study:

Neurotrophins and fetal anticonvulsant syndrome;

The role of miRNA-mediated regulation of Kv4.2 during status epilepticus;

Contribution of cortical interneurons to epilepsy;

Interaction between TrkB signaling in interneurons and epilepsy;

Potential for seizure control of isovaline in epilepsy;

Ultra High Resolution of the Hippocampus in Epilepsy.

Neurotrophins and fetal anticonvulsant syndrome

This proposal will use preclinical models of early life exposure to anti-seizure medications to test the hypothesis that multiple AEDs contribute to a common disruption in brain development underlying many of the observed AED side effects.

The role of miRNA-mediated regulation of Kv4.2 during status epilepticus

A major challenge in epilepsy research is the identification of therapeutic strategies that are beneficial for patients with epilepsy disorders of different etiologies. Potassium channels play an important role to control neuronal activity and excitability in the brain, and might thus be promising therapeutic targets. This research will analyze how a specific potassium channel, Kv4.2, a major player to limit brain activity, is controlled by a group of small RNAs. In the future, these small RNAs might be used as therapeutic tools to manipulate Kv4.2 function and modulate brain activity in epilepsy of different etiologies.

Contribution of cortical interneurons to epilepsy

Illya Kruglikov, Ph.D.Research Assistant ProfessorNew York University, School of MedicineNew York, NY, United States

Healthy brain function depends on a precise balance of excitation and inhibition. Decreasing inhibition causes runaway excitation and consequently epilepsy. Inhibition is provided by a small and diverse group of neurons called interneurons. This project addresses the contribution of different cortical interneuron types to the development of epilepsy by genetically removing a protein, which when mutated known to cause epilepsy in humans. One goal of this project is to study the type of epileptic seizures produced by affecting specific interneuron populations. Another is to understand the wiring of cortical circuits leading to seizure generation. This project will advance our understanding of the cellular and circuit mechanisms of epilepsy.

Interaction between TrkB signaling in interneurons and epilepsy

Epilepsy is a disorder characterized by recurrent seizures that arise from disruptions in neuron firing patterns that lead to excessive excitation. Understanding the cellular and molecular mechanisms that lead to hyperexcitability and spontaneous seizures is crucial to identify targets for drug development. Investigations of the cellular and molecular origins of brain hyperexcitability leading to epilepsy have identified the brain-derived neurotrophic factor (BDNF). There is extensive evidence that BDNF, signaling through its receptor TrkB, is involved in epilepsy. However, both proepileptogenic and antiepileptogenic effects have been attributed to BDNF/TrkB signaling. This study characterizes the less well-understood mechanisms by which reductions in BDNF potentiate seizure development by influencing inhibitory transmission.

Potential for seizure control of isovaline in Epilepsy

Epilepsy is a neurological disorder that affects 65 million people worldwide and is characterized by recurrent seizures. While many patients are treatable with anti-epileptic drugs (AEDs), some do not respond and others experience adverse effects. Therefore, there is considerable interest in identifying novel candidates for AED development. Here, I assess whether isovaline, an amino acid with a unique structure that attenuates seizure-like events in brain slices, has utility as a new AED in acutely and chronically seizing animals. If so, then a new class of drugs may revolve around the unique properties of this amino acid.

Ultra High Resolution DTI of the Hippocampus in Epilepsy

Epilepsy is when patients have frequent seizures. Often, there is a defect in a part of the brain causing these seizures. If the defect can be found, surgery can eliminate the seizures. However, current techniques often cannot find the defect. Diffusion imaging is a new method that looks at the microscopic motion of water in the brain. This project will use high-definition diffusion imaging in epilepsy patients to identify with greater accuracy the parts of the brain that are causing the seizures.